Diffuse reflectance imaging for non-melanoma skin cancer detection using laser feedback interferometry

We propose a compact, self-aligned, low-cost, and versatile infrared diffuse-reflectance laser imaging system using a laser feedback interferometry technique with possible applications in in vivo biological tissue imaging and skin cancer detection. We examine the proposed technique experimentally using a three-layer agar skin phantom. A cylindrical region with a scattering rate lower than that of the surrounding normal tissue was used as a model for a non-melanoma skin tumour. The same structure was implemented in a Monte Carlo computational model. The experimental results agree well with the Monte Carlo simulations validating the theoretical basis of the technique. Results prove the applicability of the proposed technique for biological tissue imaging, with the capability of depth sectioning and a penetration depth of well over 1.2 mm into the skin phantom

Three-dimensional imaging of cell and extracellular matrix elasticity using quantitative micro-elastography

Funding: Australian Research Council; Cancer Council Western Australia; Industrial Transformation Training Centre; The William and Marlene Schrader Trust of the University of Western Australia.Recent studies in mechanobiology have revealed the importance of cellular and extracellular mechanical properties in regulating cellular function in normal and disease states. Although it is established that cells should be investigated in a three-dimensional (3-D) environment, most techniques available to study mechanical properties on the microscopic scale are unable to do so. In this study, for the first time, we present volumetric images of cellular and extracellular elasticity in 3-D biomaterials using quantitative micro-elastography (QME). We achieve this by developing a novel strain estimation algorithm based on 3-D linear regression to improve QME system resolution. We show that QME can reveal elevated elasticity surrounding human adipose-derived stem cells (ASCs) embedded in soft hydrogels. We observe, for the first time in 3-D, further elevation of extracellular elasticity around ASCs with overexpressed TAZ; a mechanosensitive transcription factor which regulates cell volume. Our results demonstrate that QME has the potential to study the effects of extracellular mechanical properties on cellular functions in a 3-D micro-environment.Publisher PDFPeer reviewe

Dual-modality confocal laser feedback tomography for highly scattering medium

Combination of optical modalities is a common practice to improve the efficiency of biomedical optics systems. We propose confocal laser feedback tomography for volumetric dualmodality imaging. Two major modalities of laser Doppler flowmetry and reflectance confocal microscopy were integrated and the signal were concurrently acquired for cross-sectional and volumetric imaging, by means of a compact laser scanning system. The technique was applied to a two-layered skin tissue phantom containing a 200 µm diameter Intralipid flow channel that features functional and morphological changes at the same time. Results show the potential for concurrent three-dimensional mapping of dynamic and static inhomogeneities in a highly scattering medium which can improve contrast in non-invasive biological tissue imaging, providing a confocal image in addition to the Doppler flowmetry image

Effect of the optical numerical aperture on the Doppler spectrum in laser Doppler velocimetry

We have investigated the effect of the optical system design on the characteristics of the Doppler spectrum of a laser Doppler velocimeter, by means of a Monte Carlo simulation model. We show that numerical aperture is one of the parameters that strongly affect the full width at half maximum and signal to noise ratio of the Doppler spectrum. The profile and intensity of the enhanced backscattering of the laser beam from a diffusive rough aluminum disk surface is measured using a range of lenses with different focal lengths and the results are incorporated into the Monte Carlo model

Polarization-sensitive laser feedback interferometry for specular reflection removal

Specular reflection from the surface of targets or prepared specimens represents a significant problem in optical microscopy and related optical imaging techniques as usually the surface reflection does not contribute to the desired signal. Solutions exist for many of these imaging techniques; however, remedial techniques for imaging based on laser feedback interferometry (LFI) are absent. We propose a reflection cancellation technique based on crossed-polarization filtering that is tailored for a typical LFI configuration. The technique is validated with three experimental designs, and a significant improvement of about 40 dB in the ratio of the diffuse and specular LFI signal is observed. Applications of this principle extend from specular reflection removal to characterization of target materials in industrial to biomedical domains

Effect of the optical system on the Doppler spectrum in laser-feedback interferometry

We present a comprehensive analysis of factors influencing the morphology of the Doppler spectrum obtained from a laser-feedback interferometer. We explore the effect of optical system parameters on three spectral characteristics: central Doppler frequency, broadening, and signal-to-noise ratio. We perform four sets of experiments and replicate the results using a Monte Carlo simulation calibrated to the backscattering profile of the target. We classify the optical system parameters as having a strong or weak influence on the Doppler spectrum. The calibrated Monte Carlo approach accurately reproduces experimental results, and allows one to investigate the detailed contribution of system parameters to the Doppler spectrum, which are difficult to isolate in experiment. (C) 2014 Optical Society of Americ

Confocal laser feedback tomography for skin cancer detection

Tomographic imaging of soft tissue such as skin has a potential role in cancer detection. The penetration of infrared wavelengths makes a confocal approach based on laser feedback interferometry feasible. We present a compact system using a semiconductor laser as both transmitter and receiver. Numerical and physical models based on the known optical properties of keratinocyte cancers were developed. We validated the technique on three phantoms containing macro-structural changes in optical properties. Experimental results were in agreement with numerical simulations and structural changes were evident which would permit discrimination of healthy tissue and tumour. Furthermore, cancer type discrimination was also able to be visualized using this imaging technique

Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

Background and Purpose- There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs). Methods- We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria. Results- After reviewing 13 392 reports and communicating with certain authors of 12 published studies, a total of 52 823 acute ischemic stroke patients from 6 studies were enrolled in the present meta-analysis: DOACs: 366, warfarin: 2133, and 503 241 patients without prior anticoagulation. We detected no additional risk of symptomatic intracerebral hemorrhage following IVT among patients taking DOACs within 48 hours-DOACs-warfarin: NINDS (odds ratio [OR], 0.55 [95% CI, 0.19-1.59]), ECASS-II (OR, 0.77 [95% CI, 0.28-2.16]); DOACs-no-anticoagulation: NINDS (OR, 1.23 [95% CI, 0.46-3.31]), ECASS-II (OR, 0.87 [95% CI, 0.32-2.41]). Similarly, no additional risk was detected with no time limit between last DOAC intake-DOACs warfarin: NINDS (OR, 0.85 [95% CI, 0.49-1.45]), ECASS-II (OR, 1.11 [95% CI, 0.67-1.85]); DOACs-no-anticoagulation: NINDS (OR, 1.17 [95% CI, 0.43-3.15]), ECASS-II (OR, 0.87 [95% CI, 0.33-2.41]). There was no evidence of heterogeneity across included studies (I2=0%). We also provided the details of 123 individual cases with or without reversal agents before IVT. There was no significant increase in the risk of hemorrhagic transformation (OR, 1.48 [95% CI, 0.50-4.38]), symptomatic hemorrhagic transformation (OR, 0.47 [95% CI, 0.09-2.55]), or early mortality (OR, 0.60 [95% CI, 0.11-3.43]) between cohorts who did or did not receive prethrombolysis idarucizumab. Conclusions- The results of our study indicated that prior intake of DOAC appears not to increase the risk of symptomatic intracerebral hemorrhage in selected AIS patients treated with IVT